Immunotherapy With Autologous, Human Dendritic Cells Transfected With Carcinoembryonic Antigen mRNA

Cancer Invest. 2003 Jun;21(3):341-9. doi: 10.1081/cnv-120018224.

Abstract

Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoembryonic Antigen / adverse effects
  • Carcinoembryonic Antigen / genetics*
  • Carcinoembryonic Antigen / therapeutic use
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / therapy*
  • Dendritic Cells / physiology
  • Dendritic Cells / transplantation*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunotherapy / methods*
  • Leukapheresis
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • Recombinant Proteins / therapeutic use
  • Survival Analysis
  • Transfection / methods
  • Transplantation, Autologous* / adverse effects
  • Transplantation, Autologous* / mortality

Substances

  • Carcinoembryonic Antigen
  • RNA, Messenger
  • Recombinant Proteins